Shea 2004.

Study characteristics
Methods	Parallel trial of risperidone versus placebo
Participants	Inclusion criteria: male and female outpatients aged 5‐12 years a diagnosis of ASD or PDD according to the DSM‐4 "a total score of 30 or more on the Childhood Autism Rating Scale (CARS)". Exclusion criteria: schizophrenia other psychotic disorders clinically relevant non‐neurologic disease clinically significant laboratory abnormalities seizure disorder for which participants were receiving > 1 anticonvulsants seizure in the last 3 months Location/setting: 7 investigational sites in Canada Sample size: 79 participants Number of withdrawals/dropouts: risperidone (2 total), "1 withdrew because of an adverse event (the result of an accidental overdose on day 2) and 1 withdrew because of insufficient response". Placebo (5 total) "1 withdrew because of an adverse event (an accidental medication overdose on day 16), 2 withdrew because of insufficient response, and 2 withdrew consent." Gender: 29/40 boys (risperidone); 32/39 placebo Mean age: 7.6 years (risperidone, 7.3 years (placebo) IQ: 14 participants had IQ > 85; 10 had IQ 71‐84, 20 had IQ 50‐70, and 22 had IQ 35‐49 Baseline ABC‐I or other BoC: ABC‐I 18.9 risperidone, 21.2 placebo Concurrent and previous medications: during the trial, anticholinergics could be initiated to treat emergent extrapyramidal symptoms after the Extrapyramidal Symptom Rating Scale (ESRS) had been completed. Prohibited medications included antipsychotics other than the study medication, antidepressants, lithium, _2‐antagonists, clonidine, guanfacine, cholinesterase inhibitors, psychostimulants, and naltrexone. A single anticonvulsant and/or medications for sleep or anxiety were permitted only in the case in which the participant was already taking them at a stable dose for the 30 days before enrolment. Similar restrictions were placed on the use of behaviour intervention therapy. Medications for pre‐existing organic disorders were allowed provided that the dose and schedule of administration were kept as constant as possible.
Interventions	Intervention (risperidone) for 8 weeks: "risperidone oral solution 1.0mg/mL was administered once daily in the morning at 0.01mg/kg/day on treatment days 1 and 2 and increased to 0.02mg/kg/day on day 3. The dose could be increased from day 8 by a maximal increment of 0.02mg/kg/day. After that, the dose could be adjusted at the investigator's discretion at weekly intervals by increments/ decrements not to exceed 0.02mg/kg/day. The maximal allowable dosage was 0.06mg/kg/day. (mean dose 0.06mg/day; mean 1.48mg/day)" Comparator (placebo) for 8 weeks: 1 mg/mL once daily increasing to 0.02 mg/kg/day
Outcomes	Primary outcomes Irritability, measured using the ABC‐I subscale (Aman 1985) aggression, measured using the Nisonger Child Behavior Rating Form‐Conduct Problem subscale AEs Secondary outcomes: none reported Timing of outcome assessments: baseline, and weeks 1, 2, 3, 5, 7 and 8
Notes	Study start date: not reported Study end date: not reported Source of funding: Janssen‐Ortho Inc, Canada, and Johnson & Johnson Pharmaceutical Research and Development Conflicts of interest: none declared Trial registry: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Inadequate details
Allocation concealment (selection bias)	Unclear risk	Inadequate details
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Insufficient details
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Insufficient details
Incomplete outcome data (attrition bias) All outcomes	High risk	Used an ITT analysis (participants who had received at least 1 dose of study medication) LTFU: 2 in treatment group withdrew because of AE and 1 withdrew due to insufficient response
Selective reporting (reporting bias)	High risk	Sedation not reported as an AE
Other bias	High risk	Study authors note that measurements were made 7 times throughout the study however only baseline and endpoint data were reported.